To compare the efficacy of oral aspirin vs intravenous diazepam on succinylcholine induced postoperative myalgia

Introduction: Succinylcholine is a short acting neuromuscular blocking age nt.. It has its own side effects which includes dysrhythmias, hyperkalemia, postoperative myalgias, etc. The incidence of muscle pain ranges from 0.2 to 89% and thus the need for the study. Materials and Methods: 60 adult patients are included in this prospective , randomised , double blind study who are scheduled to undergo elective surgery under general anaesthesia. Two groups were made randomly and Patients received either oral aspirin 600mg one hour before surgery or intravenous diazepam fifteen minutes before induction. Appropriate statistical tests were applied. Results: Status of muscle pain was recorded at 1st , 6th, 12th and 24th post operative period. Myalgia at 6th, 12th and 24th hour was significantly reduced in aspirin group compared to diazepam group. No difference was seen at one hour. Conclusion: It was concluded that aspirin prevents succinylcholine induced myalgia more effectively than diazepam in postoperative period. © 2019 Published by Innovative Publication. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by/4.0/)


Introduction
Succinylcholine is the only depolarizing neuromuscular blocking agent currently in clinical use. It is characterized by quick onset and short duration of action there by providing excellent intubating conditions. However it has got its own side effects which includes dysrhythmias, hyperkalemia, postoperative myalgias, masseter spasm etc. The incidence of muscle pain ranges from 0.2 to 89%. 1 Muscle pain occurs more commonly after minor surgery, especially in women and in ambulatory patients. 2 Postoperative skeletal muscle myalgia, which is specially prominent in the muscles of the neck, back and abdomen. Myalgia localized to neck muscles may be perceived as pharyngitis by the patient and attributed to tracheal intubation by the anaesthesiologist. Muscle pain occurs most often in patients undergoing ambulatory surgery.
The theory behind postoperative skeletal muscle myalgia is not fully understood.
One theory proposes that myalgia is secondary to muscle damage by succinylcholine induced fasciculations. 2 This is supported by findings of myoglobinemia and raise in creatine kinase level following succinylcholine administration. 3 Another hypothesis suggests a possible role for prostaglandins and cyclooxygenases in Succinlycholine induced myalgia. 4 Pretreatment with a prostaglandin inhibitor is effective in reducing the incidence of myalgia. 5 Succinlycholine induced myalgia increases length of stay in hospital thereby increasing the cost of treatment. Therefore prevention of myalgia is very important.
Various agents have been attempted to decrease the postoperative muscle pain namely, Non-depolarising neuromuscular blockers, NSAIDS, benzodiazepines, phenytoin, ketorolac, vitamin E derivatives, local anaesthetics.
Aspirin belongs to NSAID group of drugs, acts by inhibiting the synthesis of prostaglandins and thereby There is inconclusive evidence that benzodiazepines decreases postoperative myalgia.
Studies shows that Diazepam has the property to decrease severity of muscle pains. 6 Hence, we conducted this study to compare the effectiveness of Aspirin and Diazepam on succinylcholine induced myalgia.

Aims and Objectives
To study the effect of oral aspirin vs intravenous diazepam in reducing succinylcholine induced myalgia.
To assess severity of fasciculations To assess severity of myalgia

Materials and Methods
After approval from Institutional Ethical Committee, this clinical study was conducted on 60 adult patients based on inclusion and exclusion criteria.

Sample size
To detect a difference of 20% myalgia between 2 groups, keeping the power at 80% and alpha error at 0.05, a minimum of 60 patients were required, presuming a success rate of 95%.
Patients were randomized to one of the two groups using computer generated random allocation chart.
Group 1: Aspirin group (30 patients) Group 2: Diazepam group (30 patients) After preanaesthetic examination, patients were explained about the procedure. Baseline serum potassium concentrations were noted. An intravenous access was secured in non-dominant limb. In the recovery room, either aspirin or diazepam was given to the study patients by nurses who were not related to the study.
Aspirin 600mg was given orally one hour prior to surgery and diazepam 0.05mg/kg intravenously was given 15 minutes before induction. Timing of the drugs given was based on the pharmacokinetic principles of the drug.
Premedication Inj. Ranitidine 50 mg and Inj. Ondansetron 4 mg IV was given. In the operating room, monitors connected and preoperative vital parameters were recorded. Anaesthesiologist unaware of the study drug given to patients administered general anaesthesia and monitored the patient subsequently.
All patients were preoxygenated with 100% oxygen. Induction with thiopentone 3-5mg/kg IV and paralysed with succinylcholine 1.5mg/kg IV Presence and degree of fasciculations were assessed on a four point scale : 7 Grade 1: No fasciculations Grade 2: Mild, fine fasciculations at the eyes, neck, face or fingers without limb movement Grade 3: Moderate fasciculations occurring bilaterally or obvious limb movement Grade 4: Severe when widespread, sustained fasciculation.
Tracheal intubation done with appropriate size endotracheal tube and maintained with air and sevoflurane supplementation with controlled ventilation. After the patient had spontaneous efforts, vecuronium was given. After completion of surgery reversal given and patient extubated.
Postoperatively all the patients were assessed for myalgia. Myalgia was defined as "muscle pain not related to surgical intervention". Following are the grades of myalgia. 8 Grade 1: Absence of muscle pain Grade 2: Stiffness limited to one area only Grade 3: Muscle pain or stiffness noticed spontaneously by the patient, which may require analgesic therapy Grade 4: Generalized, severe or incapacitating discomfort.
The incidence and severity of myalgia was recorded by a blinded observer after 1 hour, 6 hours, 12 hours and 24 hours after extubation.

Statistical analysis
Data was analyzed using SPSS 22 version software. Categorical data was represented in the form of Frequencies and proportions. Chi-square test was used as test of significance for qualitative data. Independent t-test was used as test of significance to identify the mean difference between two quantitative variables. P value (Probability that the result is true) <0.05 was taken as statistically significant.

Results
The demographic data were comparable between the groups in terms of Age, weight, ASA grade, and duration of surgery. In terms of Fasciculations there was no statistically significant difference between two groups. There was a statistically significant difference in Median and Mean scores of myalgia which was observed between two groups at 6 hour, 12 hour and 24 hours. No difference was observed at 1 hour. Higher myalgia was seen in diazepam group compared to Aspirin group. Mean potassium levels between two groups were comparable at pre operative period, 1 hour and 24 hours.

Discussion
Succinylcholine (SCh) is the only clinically available depolarizing neuromuscular blocker. It was introduced by Thesleff and Foldes and associates in 1952, drastically changed anaesthetic practice because of its quick onset and ultrashort duration of action allowed for both rapid endotracheal intubation and rapid recovery of neuromuscular strength. 9 Succinylcholine is made up of two molecules of Acetylcholine (ACh) which binds to ACh receptors present on the postjunctional area of muscle end plate, there by generating action potential. succinylcholine is not metabolized by acetylcholinesterase which is present on the postjunctional area leading to sustained depolarization of muscle end plate resulting in fasciculations. However, because the opening of perijunctional sodium channel is time limited, this Continuous and sustained depolarization ends up in muscle relaxation. SCh even though it is not metabolized by acetylchoinesterase, but it is rapidly gets hydrolsed by plasma cholin esterase, also called as pseudocholinesterase. This explains its ultrashort duration of action. The popularity of SCh has been decreased because of its adverse effects which includes dysrrhythmias, postoperative myalgia, hyperkalemia, etc. Postoperative skeletal muscle myalgia is one of the most commonly encountered adverse effect of SCh. Its incidence widely ranges between 0.2 to 89%. 1 One theory explains the reason behind myalgia is due to the initial unsynchronized and sustained contractions of adjacent muscle fibers just before it ends up in muscle relaxation. 2 This theory has been substantiated by finding myoglobinemia and there is increase in serum creatine kinase levels following administration of SCh. This unsynchronised and sustained contractio n might produce damage to the muscle fibers, thereby causing postoperative muscle pain. 10 Prevention of SCh induced myalgia is at most important in the postoperative period. This uneasiness in terms of myalgia adds to the delayed recovery of the patients, increases the length of stay in the hospital and thereby increases the cost of treatment. The first and foremost attempt to decrease the incidence and severity of postoperative skeletal muscle myalgia was pretreatment with gallamine in 1954. 11 Preoperative administration of various agents have been tried to reduce postoperative myalgia. Prior administration of a small dose of a nondepolarizing muscle relaxant is not always effective in preventing succinylcholine induced postoperative skeletal muscle pain. 12 Prostaglandins and cyclooxygenases plays an important role in the development of postoperative myalgia. Prostaglandins can cause further tissue damage and increases the pain. So to reduce the incidence and severity of myalgia, this prostaglandin mediated destructive cycle should be stopped. Pretreatment with nonsteroidal anti inflammatory agent like aspirin, a prostaglandin synthesis inhibitor has been shown to be effective in reducing the incidence as well as severity of skeletal muscle pain following succinyl choline administration.
Diazepam is one of the several agents that has been tried in reducing the incidence and severity of myalgia after succinylcholin eadministration. Diazepam has been shown to be effective in decreasing the incidence and severity of postoperative skeletal muscle pain following administration of succinylcholine. [13][14][15][16] McLoughlin C, Nesbitt GA, Howe JP 17 conducted a study on the effect of pre-operative administration of oral aspirin on Suxamethonium induced myalgia showed the use of NSAIDs especially aspirin 600mg given 1 hour prior to surgery causes a significant reduction in post operative myalgia. In our study there is a significant reduction in the postoperative myalgia at 6, 12, 24 hrs. in aspirin group compared to diazepam group.
Fahmy NR, Malek NS, Lappas DG 18 conducted a study on effects of diazepam and d-tubocurarine on Neuromuscular, circulatory and adverse effects of intravenous succinylcholine (SCh). They observed pretreatment with Diazepam prevented Postoperative myalgia associated with SCh administration.
Jan-Uwe Schreiber, Christopher Lysakowski, Thomas Fuchs-Buder, Martin R. Trame 19 conducted meta analysis    on Prevention of succinylcholine induced fasciculation and myalgia. In the above meta-analysis best efficacy was found with nonsteroidal anti-inflammatory drugs (two trials tested aspirin). Benzodiazepines had a weak but statistically significant effect on myalgia. In our study aspirin group had statistically significant reduction in postoperative myalgia compared to diazepam group and also there was no significant difference in Mean potassium levels between two groups at pre operative period, 1 hour and 24 hours.

Conclusion
Prevention of succinylcholine induced myalgia is most important and various methods have been used to prevent the same. Our study shows that oral aspirin prevents succinylcholine induced myalgia more effectively than intravenous diazepam.

Source of Funding
None.

Conflict of Interest
None.